Adrenocortical Hormones

Question 1

What are the 2 major parts of the adrenal gland?

Answer 1

outer thin cortex, inner medulla

Question 2

What are the 3 zones in the adrenal cortex? What is each of the zone responsible for producing?

Answer 2

1. zona glomerulosa: aldosterone
2. zona fasciculata: glucocorticoids
3. zona reticularis: sex hormones/ androgens

Question 3

What is the primary controller for aldosterone secretion?

Answer 3

Angiotensin II

Question 4

What is primary controller for glucocorticoid secretion?

Answer 4

ACTH

Question 5

What’s the precursor for adrenocortical hormones?

Answer 5

Cholesterol, from plasma. Esterified once it enters the cell, and stored in lipid droplets

Question 5

Which enzyme is required for cholesterol conversion to glucocorticoids/ androgens?

Answer 5

17-hydroxylase

Question 5

Which of the adrenocortical hormone has the longest half life?

Answer 5

Cortisol - highly protein bound ~ 90min
Aldosterone, not as highly protein bound, ~ 20min

Question 5

Which enzymes is responsible for the cleavage of cholesterol to pregnenolone?

Answer 5

cholesterol desmolase (rate limiting)

Question 5

Where does the conversion of cholesterol to adrenal steroids occur?

Answer 5

mitochondria or ER

Question 6

Where is adrenocortical hormone metabolized?

Answer 6

in the liver
conjugated to glucuronic acid. Freely soluble in plasma, excreted through urine

Question 7

Which is the primary mineralocorticoid secreted by the adrenal cortex?

Answer 7

Aldosterone

Question 8

What does 11-beta-hyddroxysteroid dehydrogenase type 2 have to do with mineralocorticoid activity?

Answer 8

This enzyme is found in the renal epithelium. It can convert cortisol to cortisone (cortisol has high affinity to mineralocorticoid receptors, but not cortisone)

Question 9

In what circumstances can cortisol have a substantial mineralocorticoid effect?

Answer 9

when there is a congenital absence or inhibition of 11-beta-hyddroxysteroid dehydrogenase type 2 (when you eat too much licorice), then cortisol will have a substantial mineralocorticoid effect

Question 10

What’s the MOA of aldoesterone?

Answer 10

Increased Na+ resorption, K+ excretion
- acts on the distal nephron –> collecting tubules/ducts (principal cells of the collecting tubules)
- bind to intracellular receptors
- increased # of Na/K ATPase on the basolateral membrame
- increased Na+ and K+ channels on the apical membrane
- net result = more Na+ back into the blood stream, and more K+ into the urine

Question 11

What action doe aldosterone have on the intercalated cells in the cortical collecting tubules?

Answer 11

stimulates secretion of hydrogen in exchange for Na+

Question 12

What other organs can aldosterone act on?

Answer 12

colon, sweat and salivary glands

Question 13

How is aldosterone secretion controlled?

Answer 13

Angiotensin II directly stimulates the zona glomerulosa to secrete aldosterone

Question 14

What stimulates the increase in angiotensin II?

Answer 14

activation of renin-angiotensin system
- when there is hypovolemic, hypotension

Question 15

How does K+ concentration effect aldosterone?

Answer 15

increase in K+ concentration stimulates aldosterone secretion, leading to tubular K+ secretion

Question 16

What’s the role of ACTH in aldosterone secertion?

Answer 16

If there is a chronic decrease in ACTH, aldosterone’s response to angiotensin II is diminished.
Acute increase in ACTH can increased aldosterone, but chronic increase in ACTH does not

Question 17

What are some other factors that can affect aldosterone secretion?

Answer 17

Increase in Na+ can slightly decrease aldosterone.
Increase in atrial natriuretic peptide, can decrease aldosterone

Question 18

What is the primary glucocorticoid secreted by the adrenal cortex?

Answer 18

cortisol

Question 19

How does cortisol effect metabolis?

Answer 19

Protein: decreases extrahepatic update of amino acids, catabolic, and anti-anabolic
Liver: the increased amino acid in the blood is taken up by the liver, and converted to glucose and protein

Question 20

How does cortisol effect blood glucose concentration?

Answer 20

1. increase hepatic gluconeogenesis.
   Gluconeogenesis and glycogenesis in the liver
   - makes sure there is a supply of glucose for hormones such as glucagon and epinephrine to use
2. impair peripheral tissue uptake of glucose
   Anti-insulin effect in muscles and adipose tissues
   - excess cortisol = diabetogenic

Question 21

How does cortisol affect fat metabolism?

Answer 21

has permissive effect on fatty acid mobilization during fasting
- allows other lipophilic hormones, such as growth hormone and epinephrine, to use fatty acids from lipid stores

Question 22

How does cortisol influence inflammation and immunity?

Answer 22

• decreases inflammation –> inhibits phospholipase –> decreases synthesis of arachidonic acid, precursors for other pro-inflammatory molecules such as leukotriene, prostaglandins, and thromboxane
• stabilizes the lysosomal membranes –> decreases the release of proteolytic enzymes from damaged cells
• suppresses the immune system by suppressing T cells and antibodies
• inhibit fibroblastic activity

Question 23

How is cortisol secretion controlled?

Answer 23

hypothalamus-pituitary axis –> CRH –> ACTH –> adrenal cortex
- ACTH has direct stimulatory action on the zona fasciculata (most important one) and zona reticularis
- ACTH increases conversion of cholesterol to pregnenolone, via cAMP 2nd messenger
- chronic ACTH stimulation –> hypertrophy and hyperplasia of the 2 zones, with sustained cortisol release

Question 24

What’s the negative feedback mechanism for cortisol?

Answer 24

• free cortisol has direct negative feedback on the pituitary on ACTH release, and indirect CRH release
• ACTH release = diurnal (most in the morning, least at night)

Question 25

How does stress influence ACTH?

Answer 25

High stress can override the cortisol negative feedback mechanism on ACTH release
- stressors stimulate the neuroendocrine cells of the hypothalamus to secrete CRH.

Question 26

How are the symptoms of Addison’s explained?

Answer 26

Lack of both mineral and glucocorticoids
Decrease in mineralocorticoids:
- lack of Na retention –> hypotension, hypovolemia, hyperkalemia; mild acidosis
Decrease in glucocorticoids:
- abnormal fat, protein, and glucose metabolism –> muscle weakness, hypoglycemia, impaired utilization of fats for energy
- weight loss/ decreased appetite
- poor tolerance to stress –> Addisonian Crisis

Question 27

What is aldosterone escape?

Answer 27

Even with excess amount of aldosterone, the Na+ retention will still only be transient. Increased Na+ will increased extracellular fluid volume and blood pressure, leading to pressure natriuresis and pressure diuresis , so the renal output of Na+ and water will be normal again despite excess aldosterone.

Question 28

What happens if there is excessive aldosterone?

Answer 28

hypokalemia
when severe, can lead to muscle weakness

Question 29

What happens if there no aldosterone?

Answer 29

• hyperkalemia –> cardiac toxicity
• normally, it would exchange K+ for H+ in the intercalated cells, too much K+ = little H+ = alkalosis

Question 30

How does ACTH effect the zona glomerulosa?

Answer 30

ACTH –> binds to receptor on phospholipid bilayer –> activate adenylyl cyclase –> formation of cAMP in the cytoplasm –> activates other intracellular enzymes
- activate protein kinase A –> involved in the rate limiting step of formation pregnenolone from cholesterol

Question 31

Which diuretic antagonizes the action of aldosterone?

Answer 31

spironolactone